Background/Purpose: Proliferative Lupus Nephritis (PLN) occurs in up to 50% of patients with childhood-onset systemic lupus erythematosus (cSLE).  PLN is a significant source of morbidity and can lead to end-stage renal disease. Our objectives were to examine rates of complete and partial response to treatment in the first year in a large multiethnic cohort using non-cyclophosphamide induction strategies.  

Methods: A single-centre retrospective cohort study at the Hospital for Sick Children examined partial and complete response rates at 6 and 12 months following the diagnosis of biopsy-proven PLN (WHO Class III or IV) in cSLE patients.  Patients with PLN and concomitant Class V lupus nephritis were included.  Urine protein/creatinine ratio (uPCR) and serum creatinine (Cr) were used as core renal parameters. Urinary sediment was not included due to lack of available data. Criteria for complete (CR) and partial response (PR) were adapted from the American College of Rheumatology consensus guidelines, and from the outcome measures defined in Wofsy et al (Table 1). All data were collected prospectively on standardized clinic forms and maintained in a clinical database.  Demographic, clinical, pathologic and laboratory data were analyzed. As therapeutic options have evolved over the past 30 years, results were stratified into two treatment eras, the 1st era when prednisone and azathioprine (aza)  were routinely used in the first year, and the 2nd era when prednisone and mycophenolate mofetil (MMF) were more commonly used.

Table 1: Renal Response Definitions

Complete Response	For patients with abnormal Cr,        – Normalization of Cr
	For patients with normal Cr,        – Maintenance of a normal Cr within 50% of baseline value
	uPCR <25g/mol
Partial Response	For patients with abnormal Cr,        – Normalization of Cr OR 50% improvement in Cr
	For patients with normal Cr,        – Maintenance of a normal Cr within 50% of baseline value
	For patients with uPCR >300 (nephrotic range) at baseline,        – Reduction in uPCR to <300
	For patients with uPCR ≤300        – Reduction in uPCR by 50% to final uPCR<100 OR       normalization of uPCR <25g/mol

Results: 155 patients had biopsy-proven PLN between 1983-2013.  Mean age at PLN diagnosis was 12.6±3.4 years old, and 80% were female. The cohort’s ethnic heritage was 38% Asian, 28% Caucasian, 19% Black, and 15% other. 47 (30%) patients had class III, 85 (55%) had class IV, 5 (3.2%) had III/V, and 11 (7.1%) had class IV/V.  34 (22%) patients developed acute renal failure. Other phenotypic features included malar rash (71%), arthritis (74%), fever (65%), and photosensitivity (28%). At baseline, mean C3 was 0.72, and mean C4 was 0.11. Overall, 61% had CR and 15% had PR at 6 months, while 68% had CR and 7.5% had PR at 12 months (see Table 2 for complete results). We found that the rate of CR at 6 and 12 months was significantly higher in Era 1 (aza) than in Era 2 (MMF).

Table 2: Response rates

	Overall (1983-2012) (N=150)	ERA 1 (1983-2002) (N=86)	ERA 2 (2003-2012) (N=64)	p-value
Complete response @ 6 mo (N, %)	92 (61)	59 (69)	33 (52)	0.04
Complete response @ 12 mo	101 (68) (n=149)	64 (76)	37(59) (n=63)	0.04
Partial response @ 6 mo	23 (15)	10 (12)	13 (20)	0.17
Partial response @ 12 mo	12 (7.5) (n=149)	4 (4.6)	8 (13) (n=63)	0.13

Conclusion: The majority of patients showed a complete response to treatment at 6 months, with 68% of patients demonstrating complete response by one year. Partial response rates at both 6 and 12 months were comparatively lower.  Interestingly, CR rates at 6 and 12 months were higher in the aza-prednisone era as compared to the MMF-prednisone era.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/childhood-onset-systemic-lupus-erythematosus-short-term-treatment-response-rates-in-proliferative-lupus-nephritis/